King's College Criteria for Acute Liver Failure
The primary (first) criterion of the King's College criteria differs fundamentally between acetaminophen-induced and non-acetaminophen acute liver failure cases.
Acetaminophen-Induced ALF
For acetaminophen toxicity, the first and most critical criterion is arterial pH < 7.3 after adequate fluid resuscitation, regardless of the grade of hepatic encephalopathy 1, 2, 3. This single criterion alone indicates poor prognosis and potential need for liver transplantation consideration.
- This pH criterion takes precedence over all other factors
- It applies irrespective of encephalopathy grade
- Must be measured after proper volume resuscitation to ensure accuracy
If pH ≥ 7.3, then evaluate the combination criteria:
- Prothrombin time > 100 seconds (INR > 6.5) AND
- Serum creatinine > 300 μmol/L (3.4 mg/dL) AND
- Grade III or IV hepatic encephalopathy
Non-Acetaminophen-Induced ALF
For non-acetaminophen causes, the first criterion is prothrombin time > 100 seconds, irrespective of encephalopathy grade 1, 2, 3.
If PT ≤ 100 seconds, then assess for any three of the following five criteria:
- Etiology: non-A, non-B hepatitis, halothane hepatitis, or idiosyncratic drug reactions
- Age < 10 or > 40 years
- Jaundice to encephalopathy interval > 7 days
- Prothrombin time > 50 seconds
- Serum bilirubin > 300 μmol/L
Critical Clinical Context
Important caveats about these criteria:
- The King's College criteria have acceptable specificity (82-95%) but limited sensitivity (58-68%) for predicting mortality 4, 5
- Recent evidence suggests only one-third of patients meeting these criteria actually undergo transplantation, with over 80% transplant-free survival in modern ICU settings 6
- The criteria perform best when applied to patients with high-grade (III-IV) encephalopathy 4
- Sensitivity has decreased in studies published after 2005 compared to pre-1995 studies (58% vs 85%), likely reflecting improved modern intensive care management 4
The pH criterion for acetaminophen toxicity remains the single most powerful predictor, with some studies showing that lactate levels (> 3.5 mmol/L at 4 hours or > 3.0 mmol/L at 12 hours after resuscitation) may provide additional prognostic value 1.
These criteria should prompt immediate contact with a liver transplantation center for discussion, even though modern supportive care has improved outcomes beyond what the original criteria predicted 6.